Nexavar - Kidney cancer drug gets Swiss nod

Nexavar is used for the treatment of patients with advanced kidney cancer.

BY OUR PHARMA CORRESPONDENTApril 4, 2006

Swiss Agency for Therapeutic Products (Swissmedic) has approved Nexavar (sorafenib) tablets for the treatment of patients with advanced kidney cancer, Bayer Pharmaceuticals Corporation and Onyx Pharmaceuticals, Inc. said in a press statement.

The drug is indicated in renal cell carcinoma (RCC),after nepherectomy and prior palliative or adjuvant therapy with cytokines (IL-2, IFN).

Nexavar, which has been shown to double progression-free survival in patients with advanced RCC, will be marketed by Bayer in Switzerland.

This is the first oral multi-kinase inhibitor that targets both the tumor cell and tumor vasculature. In preclinical models, Nexavar targeted members of two classes of kinases known to be involved in both tumor cell proliferation (tumor growth) and tumor angiogenesis (tumor blood supply) - two important cancer growth activities. These kinases included RAF kinase, VEGFR- 2, VEGFR-3, PDGFR-B, KIT, and FLT-3.

Nexavar has been studied in more than 20 tumor types and in nearly 8,000 clinical trial patients. It is currently in phase III clinical trials for the treatment of advanced hepatocellular carcinoma (HCC), or liver cancer, and metastatic melanoma, or skin cancer. A phase III clinical trial in non-small cell lung cancer (NSCLC) was initiated in February 2006. In addition to company-sponsored trials, there are a variety of Nexavar studies being sponsored by government agencies, cooperative groups and individual investigators.

However, the drug makers alert that based on the current, approved package insert for the treatment of patients with advanced kidney cancer, hypertension may occur early in the course of therapy and blood pressure should be monitored weekly during the first six weeks of therapy and treated as needed. Incidence of bleeding regardless of causality was 15% for Nexavar vs. 8% for placebo and the incidence of treatment-emergent cardiac ischemia/infarction was 2.9% for Nexavar vs. 0.4% for placebo. Most common treatment-emergent adverse events with Nexavar were diarrhea, rash/desquamation, fatigue, hand-foot skin reaction, alopecia, and nausea. Grade 3/4 adverse events were 38% for Nexavar vs. 28% for placebo. Women of child-bearing potential should be advised to avoid becoming pregnant and advised against breast-feeding. In cases of any severe or persistent side effects, temporary treatment interruption, dose modification or permanent discontinuation should be considered.

Nexavar is being co-developed by Bayer and Onyx. The co-development collaboration calls for Onyx to fund 50 percent of the development and marketing costs for Nexavar worldwide, except in Japan. In return, Onyx has a 50/50 profit share in the United States, where the companies co-promote the product. In all other countries (except Japan) Bayer has exclusive marketing rights and Onyx's profit share is slightly less than 50 percent. In Japan, Bayer will fund product development and Onyx will receive a royalty.

Nexavar was approved by the U.S. Food and Drug Administration (FDA) in December 2005. In September 2005, Bayer filed for regulatory approval with the European Medicines Agency (EMEA). Pending a favorable review, market availability is possible in the EU countries in the second half of 2006. In addition, Bayer has completed filings in several countries, including Mexico, Australia, Brazil, Canada, and Turkey.